title: Epigallocatechin-3-gallate effectively attenuates skeletal muscle atrophy caused by cancer cachexia.
abstract: Cachexia, also known as wasting syndrome notably with skeletal muscle atrophy, costs nearly one-third of all cancer deaths in man. (-)-Epigallocatechin-3-gallate (EGCG), the principal polyphenolic component in green tea, is a potent preventive against cachexia as well as cancers. However, how EGCG counteracts cachexia-provoked muscle wasting is unclear. EGCG was demonstrated to be able to retard tumor progression as well as to prevent body weight from loss, because EGCG attenuates skeletal muscle leukocytic infiltration and down-regulates tumor-induced NF-κB and E3-ligases in muscle. In mice, the dosages optimized against cachexia were determined to be 0.2 mg/mouse/day for prevention and to be 0.6 mg/mouse/day for treatment. Anti-cachexia effects were assessed using the LLC tumor model. Mice with the same body weight were divided into groups, including control, tumor bearing, and tumor-bearing but receiving water or EGCG in both prevention and treatment experiments. RT-PCR was used to assess mRNA expressions of NF-κB, MuRF 1, and MAFbx. The intracellular NF-κB, MuRF 1 and MAFbx were determined and quantified by immunofluorescence and Western blotting, respectively. Our results conclude EGCG regulates the expressions of NF-κB as well as downstream mediators, MuRF 1 and MAFbx, so EGCG may be an appropriate agent to be included in ensemble therapeutics of the tumor-induced muscle atrophy.
authors.affiliation: Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Ying-Jiun
authors.initials: YJ
authors.lastname: Lai
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chan
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Li
authors.forename: Chang-Jer
authors.initials: CJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis
chemical_list: D016588:Anticarcinogenic Agents; D009124:Muscle Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D002392:Catechin; C045651:epigallocatechin gallate; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases